Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO)

被引：97

作者：

He, Wu ^{[1
]}

Zhou, Bin ^{[2
,3
,6
]}

Liu, Weijia ^{[2
,3
]}

Zhang, Meizi ^{[6
]}

Shen, Zhenhua ^{[1
]}

Han, Zhifu ^{[2
,3
]}

Jiang, Qingwei ^{[1
]}

Yang, Qinghua ^{[1
,5
]}

Song, Chuanjun ^{[1
]}

Wang, Ruiyong ^{[1
]}

Niu, Tianhui ^{[2
,3
]}

Han, Shengna ^{[4
]}

Zhang, Liron ^{[4
]}

Wu, Jie ^{[1
]}

Guo, Feima ^{[6
]}

Zhao, Renbin ^{[6
]}

Yu, Wenquan ^{[1
]}

Chai, Jijie ^{[2
,3
]}

Chang, Junbiao ^{[1
,5
]}

机构：

[1] Zhengzhou Univ, Coll Chem & Mol Engn, Zhengzhou 450001, Peoples R China

[2] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China

[3] Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China

[4] Zhengzhou Univ, Basic Med Coll, Zhengzhou 450001, Peoples R China

[5] Collaborat Innovat Ctr New Drug Res & Safety Eval, Zhengzhou 450001, Henan Province, Peoples R China

[6] China Acad Space Technol, Engn Res Ctr Space Biol, Space Biol Res & Technol Ctr, Beijing 100190, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 18期

基金：

中国国家自然科学基金;

关键词：

RNA DEMETHYLASE ALKBH5; OXIDATIVE DEMETHYLATION; CRYSTAL-STRUCTURE; SUBSTRATE; DNA; RECOGNITION; REVEAL;

D O I：

10.1021/acs.jmedchem.5b00702

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with la reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases.

引用

页码：7341 / 7348

页数：8

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